There has been little recent investigation into the nature of liver cation transport. Numerous common medicatons are cationic compounds and better understanding of hepatic cation uptake and secretion could have profound clinical implications. Further characterization of hepatic cation transport is the objective of these studies. Proposed studies will investigate: 1. Normal mechanisms of biliary secretion and hepatic uptake of cations. Four cationic compounds: procaine amide ethobromide (PAEB) and glycopyrolate (quaternary amines); and propranolol and meperidine (tertiary amines) will be studied. Isolated perfused rat liver and isolated rat hepatocyte models will be utilized. Effects of concomitant administration of anions (BSP, sodium taurocholate) and agents stimulating bile flow (ethacrynic acid, ouabain) on cation transport will be assessed. 2. Cation transport during cholestasis. Recent observations in this laboratory and in other laboratories have suggested that marked differences in hepatic handling of anions and cations by the liver occur following cholestasis induced surgically by bile duct ligation or pharmacologically by ethinyl estradiol (EE) administration. Extrahepatic obstruction appears to reduce hepatic anion uptake and/or intracellular anion binding but does not alter these parameters for cations. EE appears to reduce hepatic cation uptake but does not alter initial anion disappearance. Isolated perfused livers or isolated hepatocytes will be prepared from donor rat livers subjected to previous bile duct ligation for 72 hours or EE treatment (5 mg/kg P.O. x 5 days). Rates of uptake of meperidine, propranolol and PAEB (cations) will be contrasted with those of pentobarbital and BSP (anions) using standard pharmacokinetic and Michaelis-Menton calculations.